Manipulating fluidic reagents and assessing the results of reagent interactions are central to chemical and biological science. Manipulations include mixing fluidic reagents, assaying products resulting from such mixtures, and separation or purification of products or reagents and the like. Assessing the results of reagent interactions can include autoradiography, spectroscopy, microscopy, photography, mass spectrometry, nuclear magnetic resonance and many other techniques for observing and recording the results of mixing reagents. A single experiment can involve literally hundreds of fluidic manipulations, product separations, result recording processes and data compilation and integration steps. The effects of mixing fluidic reagents are typically assessed by additional equipment relating to detection, visualization or recording of an event to be assayed, such as spectrophotometers, autoradiographic equipment, microscopes, gel scanners, computers and the like. Fluidic manipulations are performed using a wide variety of laboratory equipment, including fluidic mixing devices, centrifugation equipment, molecule purification apparatus, chromatographic machinery, gel electrophoretic equipment and various fluid heating devices.
An example of where heating devices are important is the amplification of nucleic acids which is central to the current field of molecular biology. Library screening, cloning, forensic analysis, genetic disease screening and other increasingly powerful techniques rely on the amplification of extremely small amounts of nucleic acids. As these techniques are reduced to a smaller scale for individual samples, the number of different samples that can be processed automatically in one assay expands dramatically. Microscale devices have evolved which can have few to hundreds of fluidly connected channels, conduits, chambers and wells for handling mircofluidic volumes. New integrated approaches for the handling and assaying of a large number of small samples are needed.
In particular, new integrated approaches for the precise temperature control of microfluidic volumes are needed. For example, in the polymerase chain reaction (PCR) for nucleic acid amplification, a purified DNA polymerase enzyme is used to replicate the sample DNA in vitro. This system uses a set of at least two primers complementary to each strand of the sample nucleic acid template. Initially, the sample nucleic acid is heated to cause denaturation to single strands, followed by annealing of the primers to the single strands, at a lower temperature. The temperature is then adjusted to allow for extension of the primers by the polymerase along the template, thus replicating the strands. Subsequent thermal cycles repeat the denaturing, annealing and extending steps, which results in an exponential accumulation of replicated nucleic acid products. The accuracy and reproducibility of the microfluidic analyses can be highly dependent on the temperature of the fluid volume. Robust heating devices that can accurately control the temperature of microfluidic volumes are required.
The concentration of fluids is another field where heating devices come into play. In many chemical and biochemical analysis methods performed using microfluidic devices, it is advantageous to concentrate an analyte as part of the analysis. For example, increased analyte concentration generally leads to increased chemical reaction rates, increased rates of mass transfer, and enhanced detectability.
One general problem which has not been solved for microfluidics and which the present invention presents is an integrated, reproducible, and inexpensive temperature control for heating, thermal cycling, concentration of fluids, volume measurement, sensing and fluid transport. Prior art solutions in the form of “thermofoils” attempt to solve part of this problem but they involve incorporating resistance temperature detector devices or thermistors into the film and are therefore quite expensive. It is an object of the present invention to provide low-cost heating element that is affixable to a variety of temperature-sensitive devices.